Interfacing between a CE to an ESI-MS is increasingly used in biomedical and biochemical applications with minute sample volumes and high-speed analyses. Several approaches for interfacing (i.e. establishing electrical contact at or near the end of the CE capillary) have been done.
In U.S. pat. No. Re. 34,757, 1994 (4,885,076, 1989), shows a CZE with a high voltage power supply in series with an EIS high voltage power supply spraying into an MS skimmer. Although high sensitivity and efficiency was achieved, disadvantages included (1) a dependence on the buffer system used, (2) ESI instability under some operating conditions and (3) the need to regularly replace the metal coating on the capillary tip.
In U.S. pat. No. 5,423,964, 1995 to Olivares et al., also spraying into a skimmer, a metal coating on the tip of the CE capillary made contact with a metal sheath capillary to which the CE terminus/ESI voltage was applied. In addition, a non-conductive capillary in combination with applying the EIS high voltage to a co-axial sheath flow was used. The sheath liquid, with a small electrolyte content, is infused to the ESI source through a sheath capillary surrounding the end of the separation capillary and terminating near the end of the separation capillary. The sheath liquid flowing at a few microliters per minute is added to the CE effluent as it elutes from the terminus of the CE capillary thereby providing the necessary electrical contact. The sheath-liquid interface has been widely employed, but not without shortcomings. The sheath-liquid composition must be carefully selected to avoid formation of moving ionic boundaries inside the capillary from migration of sheath-liquid counterions into the CE capillary. These ionic boundaries may cause variation in migration time and resolution. In addition, the sheath liquid incorporates impurities and other charge carrying species that can be ionized by the electrospray process and decrease overall sensitivity.
A sheathless design has been reported by SA Hofstadler, F D Swanek, J C Severs, A G Ewing and R D Smith, Rapid Commun. Mass Spectrom., "Analysis of Single Cells with Capillary Electrophoresis Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry", S. A. Hofstadler, J. C. Severs, R. D. Smith, F. D. Swanek and A. G. Ewing, Rapid Commun. Mass Spectrom., 10, 919-922 (1996), wherein the capillary terminus was tapered and coated with gold. Fabrication of the gold-coated, tapered capillaries adds time and complexity to obtaining MS results. A flow-rate minimum limit of approximately 70 nL/min has been reported for the sheathless interface with improvements obtained if run at higher flow-rates (up to 250 nL/min), Bateman, K.; Thibault, P.; White, R. presented at the 44th ASMS Conference of the American Society for Mass Spectrometry and Allied Topics, Portland, Oreg., 1996.
The paper by E. D. Lee, W. Muck, J. D. Henion and T. R. Covey, Biomed. and Env. Mass Spectrom. 18, 844 (1989), discusses a liquid junction as an interface. Electrical contact is established through a liquid reservoir surrounding the junction of the separation capillary and a "transfer" capillary. A gap between the two capillaries is adjusted to about 10-20 micrometer permitting sufficient make-up liquid from the reservoir to be drawn into the transfer capillary and avoiding anolyte loss. Of course, elecrophoretic separation is terminated at the discontinuity of the gap. The flow of make-up liquid into the "transfer" capillary is induced by a pressure difference (generally arising due to some combination of differences in height of the two ends of the capillary and the venturi effect of the nebulizing gas at the capillary tip). One of the disadvantages of the liquid junction interface is the difficulty in establishing a reproducible spacing of the capillary segments, and the fact that both the anolyte transfer efficiency and the flow rate of added liquid from the reservoir are critically dependent on this spacing.
A disadvantage of both the sheath-flow and liquid junction interfaces is the need for electrolyte added to the ESI source (emitter) to maintain the electrical circuit. This added electrolyte often decreases biological or chemical molecule detection sensitivity. And, as stated previously, disadvantages of the sheathless gold-coated, tapered capillary include the complexity of assembly, and a special terminus on the CE capillary is required. Accordingly, there is a need for CE-ESI-MS interface that is simple to assemble and operate, specifically neither requiring gold plating nor requiring added electrolyte (buffer), but permitting operating at low flow rates for a wide range of liquid compositions.